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Papers of the Week


Papers: 31 Aug 2024 - 6 Sep 2024


2024 Aug 17


Int J Mol Sci


39201645


25


16

KCNG4 Genetic Variant Linked to Migraine Prevents Expression of KCNB1.

Authors

Lacroix G, Bhat S, Shafia Z, Blunck R

Abstract

Migraines are a common type of headache affecting around 15% of the population. The signalling pathways leading to migraines have not been fully understood, but neuronal voltage-gated ion channels, such as KCNG4, have been linked to this pathology. KCNG4 (Kv6.4) is a silent member of the superfamily of voltage-gated potassium (Kv) channels, which expresses in heterotetramers with members of the KCNB (Kv2) family. The genetic variant Kv6.4-L360P has previously been linked to migraines, but their mode of action remains unknown. Here, we characterized the molecular characteristics of Kv6.4-L360P when co-expressed with Kv2.1. We found that Kv6.4-L360P almost completely abolishes Kv2 currents, and we propose that this mechanism in the trigeminal system, linked to the initiation of migraine, leads to the pathology.